Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea receptor

Chiyo Shiota, Jonathan V. Rocheleau, Masakazu Shiota, David W. Piston, Mark A. Magnuson

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Pancreatic α-cells, like β-cells, express ATP-sensitive K + (KATP) channels. To determine the physiological role of KATP channels in α-cells, we examined glucagon secretion in mice lacking the type 1 sulfonylurea receptor (Sur1). Plasma glucagon levels, which were increased in wild-type mice after an overnight fast, did not change in Sur1 null mice. Pancreas perfusion studies showed that Sur1 null pancreata lacked glucagon secretory responses to hypoglycemia and to synergistic stimulation by arginine. Pancreatic α-cells isolated from wild-type animals exhibited oscillations of intracellular free Ca2+ concentration ([Ca 2+]i) in the absence of glucose that became quiescent when the glucose concentration was increased. In contrast, Sur1 null α-cells showed continuous oscillations in [Ca2+]i regardless of the glucose concentration. These findings indicate that KATP channels in α-cells play a key role in regulating glucagon secretion, thereby adding to the paradox of how mice that lack KATP channels maintain euglycemia.

Original languageEnglish
Pages (from-to)E570-E577
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number4 52-4
DOIs
StatePublished - Oct 2005

Keywords

  • Adenosine 5′-triphosphate-sensitive potassium channel
  • Glucagon
  • Pancreas perfusion
  • Pancreatic α-cell
  • Sulfonylurea receptor 1

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